1. Field of the Invention
The present invention relates to compositions and methods for the treatment of orthopedic ailments. In accordance with one embodiment, the present invention relates to compositions and methods for treating fractured bone and/or increasing the rate of healing thereof. In accordance with such an embodiment, a nutraceutical composition that stimulates inducible nitric oxide synthase (iNOS) enhances bone fracture healing, as demonstrated by biomechanical properties. Use of the nutraceutical composition promptly after bone fracture enhances fracture healing. Further, the present invention relates to compositions, dosage forms, and methods for treating, inhibiting the onset, and/or slowing the rate of development of osteoporosis. In particular, the present invention relates to nutraceutical compositions, dosage forms, and methods for the treatment and/or prevention of osteoporosis via the up-regulation of iNOS.
2. Description of the Related Art
Bone fractures can be caused by force or pressure on a limb that exceeds the strength of the bone (e.g., flexural, torque and/or compression forces). Open or compound fractures occur when broken bone penetrates the skin, whereas in closed fractures, the skin remains intact. Fractures can be crosswise, lengthwise, and/or bones can be broken in multiple places. In addition to physical trauma, pathologic fracture of bones can be caused by disease, such as osteoporosis or bone cancer. Regardless of cause, the significant pain and dysfunction associated with bone fracture is often a life altering experience, aggravated by the long time required for bones to heal sufficiently to function normally. There has been a long felt need for medications and methods of treatment that expedite fracture healing.
Fracture healing results from a complex and sequential cascade of cellular events that restore bone to its pre-fracture condition. The space between the two ends of the fracture fill with a hematoma that is rich in mesenchymal cells and cytokines, which represents the soft callus that eventually undergoes an inflammatory phase followed by a reparative and then a remodeling phase.
Although the exact regulatory mechanisms for these phases are yet to be fully understood, neo-vascularity as well as osteoblast recruitment at the callus site appears to play a key role for successful healing.
With regard to osteoporosis, osteoporosis is a medical condition resulting in the loss of bone mass that results in the deterioration of bone architecture and an increase in the risk of fracture. Osteoporosis may occur primarily or secondarily as a result of another medical condition. Osteoporosis commonly affects both men and women age 50 years and older, although secondary osteoporosis can affect a person at any age. While there are various ways in which to treat osteoporosis there remains a need for a more simple, reliable and cost-effective way to treat those afflicted with osteoporosis.
The science behind the use of dietary supplements to treat diseases has increased over the past several decades. This includes the use of natural foods or products in combination with specific compounds. However, the biological and biochemical roles of these natural products are still being elucidated so that significant unpredictability remains for even small changes in formulations and/or depending on varying patient specific factors.
Arginine and other amino acids have been known for decades to play important roles in biological function of humans and animals in general. Ginger and other herbs are often combined in foods. A combination of rosemary with other ingredients (e.g., curcumin and quercetin) is taught in U.S. Patent Application Publication No. 2002/0051826, to Darland et al., for use in treating inflammation-related diseases. In addition to those main ingredients, Darland also suggests optionally using limonene, which can come from D-limonene or hesperidin, or the use of between 180 mg and 220 mg of ginger; the formulation can optionally include 180 mg to 220 mg of citrulline and other vitamins. Such reports suggest the safety of ingredients such as ginger, citrulline and arginine as long-term dietary supplements. While complex formulations such as those disclosed in the prior art are indicated to have general health benefits, there is a need for increased testing of specific formulations and determination of their impact, both positive and negative, on different aspects of health.
Thus, there remains substantial unpredictability in the benefits and detriments of natural herbs, with a wide range of conflicting and unreliable teachings, many based on anecdotal reports that cannot be reliably reproduced. In order to make a medical treatment recommendation, one of ordinary skill in the art of Western medical research requires data from studies that used accepted scientific methods. Such scientific methods include controls (e.g., placebo or baseline formulations), independent objective analysis, patient histories and patient monitoring before, during and after each study. Where possible, scientific methods should include double blind clinical trials and uniform compositions with reliable and consistent ingredients and analyses. Otherwise, the data and/or conclusions are subject to criticism as subjective, anecdotal, and/or wrong based on properly conducted studies, for example, studies of the type accepted by the U.S. Food and Drug Agency (US FDA), which may include an IRB protocol (Institutional Review Board protocol submitted to and approved by other scientists).
It is preferred to have study results that can be relied upon by clinicians trained in modern medicine and science. While it is desirable to use natural products that have well-established safety as foods in place of synthetic chemical pharmaceutical formulations, such use must be based on sufficient studies to justify replacing or supplementing medicines that have met regulatory and scientific scrutiny. The present inventors were challenged by the problems of finding compositions and methods for treatment and inhibition of osteoporosis that are practical for long-term routine administration (while avoiding side effects of existing formulations), enable treatment of and prevention of osteoporosis in patients that cannot utilize prior osteoporosis treatments, and/or provide new practical and cost-effective compositions to prevent as well as treat osteoporosis.